Our research efforts are directed toward investigating the effect and mode of action of hormones and xenobiotics on the regulation of enzyme patterns during perinatal development. Particular emphasis has been placed on the postnatal development of hepatic histidase in the rat following gestational exposure to diethylstilbestrol (DES) and other hormonally-active xenobiotics. Histidase of the rat undergoes a complex postnatal developmental course, in which its catalytic activity appears shortly following parturition and subsequently rises in a multiphasic sex specific fashion, resulting in enzyme levels which are considerably higher in the adult female than the male. Recent experiments demonstrate that prenatal exposure to DES results in no change of hepatic histidase activities in immature male and female offspring and adult male offspring. However, histidase activities of adult female rats were decreased by 30% and approached activities of adult males. Thus, DES elicits a prenatal programmed response of hepatic histidase. Since sexual differences in heptic metabolism are believed to be regulated by the hypothalamic-pituitary axis, we suggest that DES affects the developing brain and thus metabolic potential in mature animals. BIBLIOGRAPHIC REFERENCE: Lamartiniere, C. A., Bridges, E. and Lucier, G. W.: Fetal programming of hepatic histidase by diethylstilbestrol. Fed. Proc. 36, 927, 1977.